The overall research objectives are to determine the humoral mechanisms in the regulation of pulp circulation. Microcirculatory methods will be applied with the aim of characterizing pulp hemodynamics at the organ level, and microcirculatory methods at the local level. The effects of various humoral interventions (acetylcholine, bradykinin, histamine and serotonin) on macrocirculatory and microcirculatory dynamics will be determined. Macrocirculatory measurements of blood flow will be made with the uses of both the Xenon-133 washout and the radioactive microsphere (15 micrometers) methods in dogs. Microcirculatory studies will be conducted in the rodent pulp with microscopic determinations of the following parameters in single unbranched microvessels in microvascular network of the pulp. These include the red cell velocity with the use of the "two-slit" photometric technique, the distribution of volumetric flow and the vascular pattern. Interactions between the humoral substances and the autonomic nervous system on pulp hemodynamics will also be investigated by the simultaneous application of both stimuli. The macrocirculatory and microcirculatory findings under various humoral alterations will be correlated. This project, with the use of newly developed hemodynamic methods, will allow us to evaluate systematically the humoral mechanisms of the regulation of pulp circulation. In addition, the fundamental information provided by this project will be used to elucidate the pathophysiological mechanisms of pulp disorders, e.g. pulpitis in future investigations.